3^rd Antibodies and Bio Therapeutics Congress & B2B November 08-09, 2017 Las Vegas, Nevada, USA

Antibody engineering is a great tool for improving antibody functions and immunogenicity improvement. Engineered therapeutic antibodies are better for affinity maturation, specifically by improving on-rate of the antibody binding affinities. The need to overcome the immunogenicity problem of rodent antibodies in clinical practise has resulted in a plethora of strategies to isolate human antibodies.

The evidence indicates that two simian immunodeficiency viruses (SIV), one from Chimpanzees (SIVcpz) and the other from sooty mangabeys (SIVsm), crossed the species barrier to humans, generating HIV-1 and HIV-2, respectively. The importance of characterizing the prevalence, geographic distribution, and genetic diversity of naturally occurring SIV infections to investigate whether humans continue to be exposed to SIV and if such exposure could lead to additional zoonotic transmissions. Through vigorous efforts made in the past two centuries, public health workers have succeeded in developing vaccines, antibiotics, and chemotherapeutics, and as a result most infectious diseases have been brought under control in industrialized countries. However, in developing countries, infectious diseases have been harder to contain, and the increase in migration and movement of populations in the last two decades has made national boundaries disappear as far as the transmission of infection is concerned. Some diseases, such as malaria, have been eradicated from industrialized countries mainly through extensive work on vector control, but their presence in developing countries has increased because of neglect or drug resistance. One of these proteases (Histidine Aspartic Protease, HAP) is homologous to three other aspartic proteases involved in hemoglobin metabolism but has a histidine in place of one of the two aspartic acids involved in catalysis.
 

Auto-antibody is an antibody formed in response to, and reacting against, an antigenic constituent of the individual's own tissues. Several mechanisms may trigger the production of autoantibodies: an antigen, formed during fetal development and then sequestered, may be released as a result of infection, chemical exposure or trauma, as occurs in autoimmune thyroiditis, sympathetic uveitis and aspermia; there may be disorders of immune regulatory or surveillance function.      
 

Monoclonal antibody therapy is a process in which monoclonal antibodies (mAb) are used to bind monospecifically to certain cells or proteins. This may then stimulate the patient's immune system to attack those cells. Alternatively, in radioimmunotherapy a radioactive dose localizes on a target cell line, delivering lethal chemical doses. More recently antibodies have been used to bind to molecules involved in T-cell regulation to remove inhibitory pathways that block T-cell responses, known as immune checkpoint therapy. It is possible to create a mAb specific to almost any extracellular/ cell surface target. Research and development is underway to create antibodies for diseases (such as rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, Ebola and different types of cancers).     

Antibodies are used extensively as diagnostic tools in many different formats. The term applied for antibody based diagnostic tests is “immunoassay”. Antibody-based immunoassays are the most commonly used confirmatory diagnostic assays and is the fastest growing technologies for the analysis of biomolecules. Trends in antibody based diagnosis show advances in assay specificity, detection technologies and sensitivity. Sensitivity and specificity is ensured depending on whether or not the antigen to be quantified competes with labeled antigen for a limited number of antibody binding sites. Monoclonal antibodies are now widely used in all areas of biological and medical research as well as in clinical diagnostic tests and in therapy. This review concentrates on the clinical use of antibodies in therapy particularly with regard to the properties of the antibodies which seem most relevant to their usefulness. In-vitro tests using human effector systems and in-vivo animal models have demonstrated the importance of the antibody isotype and valency for antigen as well as the specificity of binding.

Antibody therapies are the most successful immunotherapy, treating a wide range of cancers. Antibodies are proteins produced by the immune system that bind to a target antigen on the cell surface. In normal physiology the immune system uses them to fight pathogens. Each antibody is specific to one or a few proteins. Those that bind to cancer antigens are used to treat cancer. Cell surface receptors are common targets for antibody therapies. Among the most promising approaches to activating therapeutic antitumor immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumors co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumor antigens. Because many of the immune checkpoints are initiated by ligand–receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunetherapeutics to achieve US Food and Drug Administration (FDA) approval.

Biosimilars and biobetters industry is likely to become a lot more dynamic and strategic than we’ve seen with small molecule generics; there will begin to become a premium on flexibility and willingness to take chances in an ever-shifting competitive and regulatory environment. The approval of the first biosimilar in the US is expected to save the healthcare industry and patients $5.7 billion over the next decade. The US biosimilars market is expected to reach $2 billion by 2018 and with the first biosimilar approved recently in America, this is an exciting time for the biosimilar field with approval in the US expected to increase during the next ten years. The regulatory landscape is evolving rapidly so it is important to understand the developments in the biosimilar guideline framework and the cohesion in legislation between the US and Europe. Key factors driving market growth include patent expiries of key biological drugs, cost containment measures from governments, aging population, and supporting legislations. The recent establishment of regulatory guidelines for biosimilars in the US is expected to add further momentum to the growth of the global biosimilars market. Increasing pressure from governments and insurers for greater biologic competition, there exists an incredible opportunity for biosimilar producers to capitalise on what is set to become the fastest growing sector of the pharmaceutical industry. 

Conventional anticancer therapeutics often suffer from lack of specificity, resulting in toxicities to normal healthy tissues and poor therapeutic index. Antibody-drug conjugates (ADCs) constitute a therapeutic modality in which a cytotoxic agent is chemically linked to an antibody (Ab) that recognizes a tumor-associated antigen. The basic strategy underlying ADC technology is to combine the target selectivity of mAbs with the potency of cytotoxic agents, such as certain natural products and synthetic molecules, with the goal of generating therapeutic drugs that are highly efficacious but also safe. The ADC platform currently includes a growing repertoire of cytotoxic payloads, linker technologies and conjugation methods. Two ADCs have recently received FDA approval and more than 30 are in clinical development. This meeting aims to highlight advances in ADC research, clinical development and regulatory perspectives.

The outlook for therapeutic antibodies is very promising. This meeting will highlight current trends in development including identifying and validating novel targets, improving drug-like properties, employing immunotherapy approaches and advancing novel constructs. This program has consistently recruited top thought leaders in the field to review the status of myriad innovative antibodies and key ideas for advancing them towards the clinic. The immune system has evolved to fight infection, and the response to microbial infection involves the activation of a complex network in which numerous cell types, soluble factors and adhesion molecules of the host immune system participate. It is therefore not possible to produce a good textbook in immunology without any reference to infection or infectious agents. Immunology, Infection, and Immunity has been produced with this in mind, and the Editors have clearly done this with an appreciation of the immune system as a defence system.          
 

Anticancer antibodies  has created great interest in antibody-based therapeutics for hematopoietic malignant neoplasms and solid tumors. Given the likelihood of lower toxic effects of antibodies that target tumor cells and have limited impact on nonmalignant bystander organs vs small molecules, the potential increased efficacy by conjugation to radioisotopes and other cellular toxins, and the ability to characterize the target with clinical laboratory diagnostics to improve the drug's clinical performance, current and future antibody therapeutics are likely to find substantial roles alone and in combination therapeutic strategies for treating patients with cancer. Therapeutic antibodies have become a major strategy in clinical oncology owing to their ability to bind specifically to primary and metastatic cancer cells with high affinity and create antitumor effects by complement-mediated cytolysis and antibody-dependent, cell-mediated cytotoxicity (naked antibodies) or by the focused delivery of radiation or cellular toxins (conjugated antibodies).

Cancer immunotherapy—treatments that harness and enhance the innate powers of the immune system to fight cancer—represents the most promising new cancer treatment approach since the development of the first chemotherapies in the late 1940s. Because of the immune system’s extraordinary power, its capacity for memory, its exquisite specificity, and its central and universal role in human biology, these treatments have the potential to achieve complete, long-lasting remissions and cancer cures, with few or no side effects, and for any cancer patient, regardless of their cancer type. Immunotherapy is treatment that uses your body's own immune system to help fight cancer. These treatment modalities are all based on destroying cancer cells by burning them (irradiation), poisoning them (chemotherapy) or removing them (surgery). While they can effectively kill or remove cancer cells, the use of these treatments often is limited because large numbers of healthy cells also tend to be destroyed. This often results in extreme morbidity and/or disfigurement of the patients treated with them.

The first monoclonal antibodies were typically made entirely from mouse cells. One problem with this is that the human immune system will see these antibodies as foreign (because they’re from a different species) and will mount a response against them. In the short term, this can sometimes cause an immune response. In the long term, it means that the antibodies may only work the first time they are given; after that, the body’s immune system is primed to destroy them before they can provide treatment. This study presents a technology that generates stable, soluble, ultra-humanized antibodies via single-step CDR redundancy minimization. Lead clones demonstrated high stability, with affinity and specificity equivalent to, or better than, the parental immunoglobulin. This significantly lowered non-human sequence content, minimized t- and b-cell epitope risk in the final molecules and provided a heat map for the essential non-human CDR residue content of antibodies from disparate sources. Antibody humanization uses multiple sequence segments derived from variable (V) regions of unrelated human antibodies, unlike other technologies that typically use a single human V region framework as acceptors for complementarity determining regions (CDRs) from starting antibodies (typically rodent). Through careful selection of human sequence segments and the application of in silico tools, CD4+ T cell epitopes are avoided so the risk of immunogenicity is reduced compared to standard humanized antibodies whilst antibody affinity and specificity is maintained. Immunogenicity assessment technology is used to confirm T cell epitopes have been removed.

The development of cancer therapies is increasingly dependent on our understanding of tumor biology, and biomarkers—especially predictive biomarkers—are crucial tools in the field of personalized medicine and health economics, in particular, as they enable definition of the populations of patients who are most likely to benefit from targeted therapies. More-effective patient selection than is possible at present is mandatory to improve the success rate of new therapies, which are sometimes prohibitively expensive, and thereby increase their cost–utility; thus, delineating reliable predictive biomarkers is essential if we are to achieve this objective. One commonly used definition of a biomarker is a measurable indicator that is used to distinguish precisely, reproducibly and objectively either a normal biological state from a pathological state, or the response to a specific therapeutic intervention. In fact, biomarkers are used for numerous purposes: to predict survival (prognostic biomarkers); to assess drug safety and evaluate target engagement and the immediate consequence on biological processes (pharmacodynamics biomarkers), to identify patients who are more likely to benefit from a treatment (predictive biomarkers; more generally termed companion biomarkers when associated with a specific therapeutic agent); to predict outcome given the response to therapy (surrogate biomarkers); and to monitor disease progression or therapeutic efficacy (monitoring biomarkers). Identification and widespread use of biomarkers will help ensure that patients receive the best possible therapeutic strategies, thereby avoiding unnecessary treatments and associated toxicities, and eventually reducing total health costs.

Biopharmaceuticals is one of the fastest growing segments in the pharmaceutical industry. They have a vital use in the treatment of chronic diseases and also result in high profit margins for the drug developers. There are several therapeutic areas for which biopharmaceuticals are being investigated; these include oncology, metabolic disorders, viral infections, genetic disorders and immunological disorders

BioTherapeutics is focused on developing innovative antibody-based cancer treatments, based on a range of proprietary technologies. These target a number of oncology indications, with a particular focus on cancers with limited treatment options. These include a mixture of solid and liquid malignancies, such as acute myeloid leukemia and breast, ovarian and lung cancers. Monoclonal antibodies have emerged as a class of novel oncology therapeutics. 

The modular structure of antibodies has enabled the customization and engineering of high affinity binders in a variety of ways. Before discussing the technologies developed for the design and discovery of antibody fragments. Antibody engineering technologies have surpassed many of the challenges imposed by the selection of antibodies using murine cell lines (i.e., hybridoma technology), eliminating the need for humanization by enabling the production of fully human antibodies in vitro or in other engineered animal models. 

Antibody conjugates are a diverse class of therapeutics consisting of a cytotoxic agent linked covalently to an antibody or antibody fragment directed toward a specific cell surface target expressed by tumor cells. The notion that antibodies directed toward targets on the surface of malignant cells could be used for drug delivery is not new.

Next-generation sequencing (NGS) provides a quantitative approach to measuring the diversity and distribution of antibody libraries. It will introduce and enable researchers on how to design, analyze, and perform antibody NGS studies and how these can be applied for discovery and engineering of monoclonal antibodies from both synthetic and immune libraries. 

Therapeutic proteins and monoclonal antibodies (MAb) have transformed biotechnology and the pharmaceutical industry. Together they form the largest part of the rapidly growing biologics drug market. Protein-based drugs include blood factors, thrombolytic agents, hormones, hematopoietic growth factors, interferons, interleukins, tumor necrosis factor, and therapeutic enzymes. 

New biotherapeutics formats are flooding the discovery and development pipelines and with this comes an increasing need for better and faster characterization tools and strategies, and improved biomolecular and biophysical assays for the new biotherapeutics.